Theophyllin compound.



UNITED STATES PATENT oFFIoE;

REINHOLD GRUTER, OF OHARLOTTENBURG, GERMANY, ASSIGNOR TO OHEMISCHE WERKE VORM. DR. HEINRICH BYK, OF GHARLOTTENBURG,GERMANY, A CORPORATION OF GERMANY.

THEOPHYLLIN COMPOUN D.

Specification of Letter's Patent.

Patented April 20,- 1909.

I To all whom it may concern:

Be it known that I, REINHOLD GRUTER, a subject of the German Emperor, residing at Oharlottenburg, Germany, have inventeda certain new and useful Theophyllin Oompound, of which the following is a specification.

Theophyllin, a therapeutically valuable roduct, is so difficult of absorption by the uman organism, that it has already been attem ted to convert this base into soluble dou le-compounds. Such compounds are for instance the well-known double salts consisting of the sodium salt of theophyllin on the one hand and sodium-salts of carboxylic acids on the other hand. Owing to the strongly pronounced hydrolytic properties of the sodium-salt of theophyllin, the double salts have, however, a strongly alkaline reaction. This defect has induced me to search for compounds with weaker bases, the princi al object being, to roduce compounds w 'ch may be applied y subcutaneous injection, a method of a plication which is new for diuretics. A subcutaneous diuretic should however not roduce irritation, and should therefore not e strongly alkaline like the compounds already known. Moreover, a subcutaneous'remedy which must be administered in the quantities necessary in case of theophyllin, should be easily soluble in water, in order that there uired dose may be introduced in a few cu ic centimeters. I have discovered, that theophyllin forms with the primary and secondary aliphatic diamins compounds which answer all these requirements, the said material bein used in the proportion of one molecule of't eophyllin to one molecule of the ali hatic amin. ,That theophyllin forms suc permanent compounds in a solid crystalline form, could not e expected, especially as theobromin, which is isomeric with theo hyllin and generally forms similar double sa ts, does not form analogous compounds, and as theophyllin itself does not act on aromatic 'amins, nor does it combine with tertiary aliphatic amins, and the heterocyclic antipyrin does' not combine with theophyllin. v

For producingrthe new compounds, the

components are caused to act u on each other undiluted or after having een dissolved in a suitablesolvent. The desired compounds maythen be obtained in a solid form by evaporation of the liquid, preferably in 'vacuo at ordinary temperature. According to the nature of the diamins, the desired compounds may be obtained also with a slightly smaller quantity of diamin, than that corresponding to one molecule, as mentioned above. The desired compounds may be produced also by mutual decomposition of salts, such as sodium-theophyllin-and hydrochloride of diamins.

Examples.

I.- 194 grams of crystallized piperazin are melted on a water-bath and then 198 grams of theophyllin introduced into the same with the aid of stirring. The latter thereby enters intosolution, and the new product separates out in a crystallized form. It may then be dried, referably \over caustic lime at ordinary or s ightly reducedpressure The equation illustrating the process of this example is as follows:

II. 198 grams of theophyllin are dissolved with a'10 per cent. solution of ethylene. diamin corresponding in quantity to 46 grams of anhydrous diamin, and the solution is evaporated over caustic soda in a vacuum of 40 centimeters; the product crystallizes out gradually and completely; its solubility in water is upward of 30 per cent.

The equation illustrating the process of 1 this example is as follows:

The new compounds are white, very soluble 1n cold and hot water. The solubility in water is about 40 per cent.'. In alcohol and ether they are less soluble.

They have no well-defined melting point, because on heating they are split up into their components. They are decomposed by strong and weak acids, even carbonic acid. If, for instance, carbonic acid or air containing carbonic acid is conducted through a solution of such compounds, free theophyllin separates out in the shape of needles characteristic of theophyllin. The new compounds have diuretic properties.

What I claim is .1. The process for the manufacture of easily soluble double compounds of theophyllin and aliphatic diamins, which consists in causing the said aliphatic diamins and theophyllin to interact in molecular proportions, substantially as described.

2. The process for the manufacture of easily soluble double compounds of theophyllin and aliphatic diaminsywhich con sists in dissolving the theophyllin in the liquid diamin in molecular proportions and drying the product over a drying substance, substantially as described.

3. The

easily solu 1e double compounds of theophyllin and aliphatic diamins, which consists in dissolving the theophyllin in an aqueous solution of the said diamin and evaporating the solution in cacao over a drying substance, substantially as described. I

4. The herein described new double compounds of theophyllin with aliphaticdiamins, the said compounds forming white crystals, very soluble in water, less soluble in alcohol and ether, capable of being decomposed by acids, while yielding theophyllin, split up into their components by heating, and having diuretic properties.

In witness whereof I have set my hand hereunto in the presence of two subscribing witnesses.

.REINHOLD GRUTER.

Witnesses PAUL SCHULTZE, ll/IAX MAETsoHKE. 

